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Feasibility of Localized Metabolomics in the Study of Pancreatic Islets and Diabetes.

ABSTRACT: (1) Background: Disruption of insulin production by native or transplanted pancreatic islets caused by auto/allo-immunity leads to hyperglycemia, a serious health condition and important therapeutic challenge due to the lifelong need for exogeneous insulin administration. Early metabolic biomarkers can prompt timely interventions to preserve islet function, but reliable biomarkers are currently lacking. We explored the feasibility of "localized metabolomics" where initial biomarker discovery is made in aqueous humor samples for further validation in the circulation. (2) Methods: We conducted non-targeted metabolomic studies in parallel aqueous humor and plasma samples from diabetic and nondiabetic mice. Metabolite levels and associated pathways were compared in both compartments as well as to an earlier longitudinal dataset in hyperglycemia-progressor versus non-progressor non-obese diabetic (NOD) mice. (3) Results: We confirmed that aqueous humor samples can be used to assess metabolite levels. About half of the identified metabolites had well-correlated levels in the aqueous humor and plasma. Several plasma metabolites were significantly different between diabetic and nondiabetic animals and between males and females, and many of them were correlated with the aqueous humor. (4) Conclusions: This study provides proof-of-concept evidence that aqueous humor samples enriched with islet-related metabolites and representative of the immediate islet microenvironment following intraocular islet transplant can be used to assess metabolic changes that could otherwise be overlooked in the general circulation. The findings support localized metabolomics, with and without intraocular islet transplant, to identify biomarkers associated with diabetes and islet allograft rejection.

SUBMITTER: Alcazar O

PROVIDER: S-EPMC6835460 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Feasibility of Localized Metabolomics in the Study of Pancreatic Islets and Diabetes.

Alcazar Oscar O Hernandez Luis F LF Tschiggfrie Ashley A Muehlbauer Michael J MJ Bain James R JR Buchwald Peter P Abdulreda Midhat H MH

Metabolites 20190929 10

(1) Background: Disruption of insulin production by native or transplanted pancreatic islets caused by auto/allo-immunity leads to hyperglycemia, a serious health condition and important therapeutic challenge due to the lifelong need for exogeneous insulin administration. Early metabolic biomarkers can prompt timely interventions to preserve islet function, but reliable biomarkers are currently lacking. We explored the feasibility of "localized metabolomics" where initial biomarker discovery is ...[more]

PMID: 31569489

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Project description:INTRODUCTION: With the shortage of donor organs for islet transplantation, insulin-producing cells have been generated from different types of stem cell. Human fetal pancreatic stem cells have a better self-renewal capacity than adult stem cells and can readily differentiate into pancreatic endocrine cells, making them a potential source for islets in diabetes treatment. In the present study, the functions of pancreatic islets derived from human fetal pancreatic progenitor cells were evaluated in vitro and in vivo. METHODS: Human pancreatic progenitor cells isolated from the fetal pancreas were expanded and differentiated into islet endocrine cells in culture. Markers for endocrine and exocrine functions as well as those for alpha and beta cells were analyzed by immunofluorescent staining and enzyme-linked immunosorbent assay (ELISA). To evaluate the functions of these islets in vivo, the islet-like structures were transplanted into renal capsules of diabetic nude mice. Immunohistochemical staining for human C-peptide and human mitochondrion antigen was applied to confirm the human origin and the survival of grafted islets. RESULTS: Human fetal pancreatic progenitor cells were able to expand in medium containing basic fibroblast growth factor (bFGF) and leukemia inhibitor factor (LIF), and to differentiate into pancreatic endocrine cells with high efficiency upon the actions of glucagon-like peptide-1 and activin-A. The differentiated cells expressed insulin, glucagon, glucose transporter-1 (GLUT1), GLUT2 and voltage-dependent calcium channel (VDCC), and were able to aggregate into islet-like structures containing alpha and beta cells upon suspension. These structures expressed and released a higher level of insulin than adhesion cultured cells, and helped to maintain normoglycemia in diabetic nude mice after transplantation. CONCLUSIONS: Human fetal pancreatic progenitor cells have good capacity for generating insulin producing cells and provide a promising potential source for diabetes treatment.

Dataset Information

Feasibility of Localized Metabolomics in the Study of Pancreatic Islets and Diabetes.

Publications

Feasibility of Localized Metabolomics in the Study of Pancreatic Islets and Diabetes.

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